The present invention relates to a novel ASPP2 splicing variant, more particularly a nucleic acid sequence and an amino acid sequence derived therefrom, for use as a marker for diagnosing cancer.
In general, the term “cancer” covers both solid tumors and malignant hemoblastoses. Since cancer is the second most common cause of death after diseases of the cardiovascular system in most industrial countries, the diagnosis and treatment of cancer is of very high medical, economical and also social and sociopolitical importance.
Cancers have a varied and often multifactorial etiology. They can affect all organs of the human body or arise from the corresponding tissues. Consequently, cancers are very heterogeneous even at the cellular level, and this often makes diagnosis thereof difficult.
With regard to tissue morphology, cancers are differentiated between solid tumors and, as in the case of hemoblastoses, individual cells which are separated from one another.
One of the most common hemoblastoses is acute myeloid leukemia. This is a disease of the hematopoietic system which leads to a strong increase in immature blood-cell precursors in bone marrow and, frequently, also in blood.
Whereas the treatment of solid tumors is therapied in the vast majority of cases by means of surgical removal in combination with radiation therapy, hemoblastoses such as acute myeloid leukemia are treated by chemotherapy, possibly supported by bone marrow transplantation.
A known problem in the chemotherapy of acute myeloid leukemia is the response to the chemotherapy, which is sometimes very diverse. For instance, for a particular proportion of patients, increased therapy refractoriness with respect to chemotherapeutics can be observed. This is associated with a distinctly worsened chance of recovery.
A further problem, which equally affects cancer types involving solid tumors and hemoblastoses, is the problem of minimal residual diseases. In the case of therapy in terms of surgical removal, radiation therapy or chemotherapy, individual cancer cells may remain in the body of the patient and possibly, after a certain latency time, lead to a recurrence of cancer. Since such minimal residual diseases nullify the success of therapy as a whole, considerable attention is also paid to their identification in cancer diagnostics.
Such diagnostics are based, as is also the case for general cancer diagnostics, mostly on DNA- or RNA-determining assays which make it possible to detect genetic aberrations characteristic of cancer cells or of the development of cancer. In addition, immunological tests which make it possible to detect cancer cell-specific markers on the cell surface or in the cytoplasm are also used. Other methods applied in cancer diagnostics are based on the detection of aberrant transcription profiles of cancer cells in relation to healthy cells of the tissue of origin.
Such diagnostic methods can lead to specific therapy if the altered transcription profiles provide information about the etiology or genetics of the particular cancer.
In the context of such diagnostic analysis, various markers are measured with regard to their presence or nonpresence or their intracellular concentration. In cancer diagnostics, both nucleic acid and amino acid sequences are used as markers, which can be detected by means of appropriate methods. At the genetic level, the markers can be detected by specific amplification and/or binding of labeled probes, whereas at the protein level, detection is achieved, for example, by means of antibodies which bind specifically.
For example, US2002/0086384 A1 describes a range of transcripts and proteins which arise as a result of alternative splicing and which can be used as markers in the context of cancer diagnostics.
However, many of the known markers, seen individually, do not make reliable diagnosis possible. There is therefore a need for additional, reliable markers for the definite diagnosis of cancer.